Central nervous system tuberculosis: An overview

INTRODUCTION — Forms of central nervous system (CNS) infection due to Mycobacterium tuberculosis include meningitis, tuberculoma, spinal arachnoiditis, and transverse myelitis.

The epidemiology and pathogenesis of CNS tuberculosis (TB) are reviewed here, as are clinical issues related to tuberculoma, spinal arachnoiditis, and transverse myelitis. Clinical issues related to tuberculous meningitis are discussed separately. (See "Tuberculous meningitis: Clinical manifestations and diagnosis".)

Issues related to management of CNS TB are discussed separately. (See "Central nervous system tuberculosis: Treatment and prognosis".)

Issues related to pulmonary TB and miliary TB are discussed separately. (See "Pulmonary tuberculosis: Clinical manifestations and complications" and "Diagnosis of pulmonary tuberculosis in adults" and "Epidemiology and pathology of miliary and extrapulmonary tuberculosis".)

Issues related to treatment of TB are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection" and "Treatment of drug-resistant pulmonary tuberculosis in adults".)

Issues related to treatment of TB in patients with human immunodeficiency virus (HIV) infection are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults with HIV infection: Initiation of therapy" and "Treatment of pulmonary tuberculosis in adults with HIV infection: Follow-up after initiation of therapy".)

EPIDEMIOLOGY — Among patients with tuberculosis (TB), approximately 1 to 5 percent are complicated by central nervous system (CNS) TB [1-11]. Therefore, in regions where the prevalence of TB is high and the prevalence of postprimary dissemination is common among children and young adults, all three forms of CNS TB (tuberculous meningitis, intracranial tuberculoma, and spinal tuberculous arachnoiditis) are encountered relatively frequently [1-11].

In regions where the prevalence of TB is low, such as North America and Western Europe, extrapulmonary manifestations of TB are observed primarily in adults with reactivation disease, and the predominant form of CNS disease is meningitis. In the United States in 2018, there were 1828 cases of extrapulmonary tuberculosis, of which 3.8 percent involved the meninges [12].

HIV is an important risk factor for CNS TB [1,13-15]. Among patients with TB, those with HIV infection have a five-fold increase in the likelihood of having CNS involvement and disseminated TB compared with those without HIV infection; this risk increases among patients with CD4 count <100 cells/microL [1].

PATHOGENESIS — During the bacillemia that follows primary infection or late reactivation tuberculosis (TB), scattered tuberculous foci (tubercles) are established in the brain, meninges, or adjacent cranial bone. (See "Tuberculosis: Natural history, microbiology, and pathogenesis".)

The establishment of a cortical or meningeal tubercle (Rich focus), with subsequent rupture into the subarachnoid space, is the critical event in the development of TB meningitis [16]. The widespread and dense distribution of foci seen in association with progressive miliary TB greatly increases the chance that juxta-ependymal tubercles will be established. (See "Epidemiology and pathology of miliary and extrapulmonary tuberculosis".)

The spillage of tubercular bacilli and tubercular protein into the subarachnoid space produces an intense hypersensitivity reaction, giving rise to inflammatory changes that are most marked at the base of the brain. Three features dominate the pathology and explain the clinical manifestations [16,17]:

●Thick gelatinous exudate, most marked at the basal part of the brain, eventually produces a fibrous mass that encases adjacent cranial nerves and vessels of Circle of Willis, leading to cranial nerve palsies and periventricular infarcts, respectively.

●Tuberculous vasculitis with resultant inflammatory vascular changes leads to spasm, constriction, thrombosis, and occlusion of intracerebral vessels. Occlusion of cerebral arteries results in infarction of the brain parenchyma. Infarcts in tuberculous meningitis are typically small, multiple, bilateral, and frequently located in the periventricular regions. The most involved structures are the basal ganglia, thalamus, and internal capsule. Periventricular infarcts are ascribed to arteritis of deep penetrating vessels of Circle of Willis, particularly the lenticulostriate arteries [18,19]. Multiple lesions are common and a variety of stroke syndromes may result; the basal ganglia, cerebral cortex, pons, and/or cerebellum may be involved [20].

Approximately one-third of patients with tuberculous meningitis present with or develop stroke (of two-thirds experience focal neurologic deficits) [21].

Intracranial vasculitis is a common feature in autopsy studies, and a major determinant of residual neurologic deficits. In one autopsy study including 27 patients, for example, phlebitis and varying degrees of arteritis were demonstrated in 22 cases, including 8 patients with associated hemorrhagic cerebral infarction [22].

●Hydrocephalus eventually develops in the majority of patients with tuberculous meningitis. Communicating hydrocephalus results from extension of the inflammatory process to the basilar cisterns and impedance of cerebrospinal fluid circulation and resorption. Noncommunicating or obstructive hydrocephalus caused by obstruction of the aqueduct develops less frequently, from contraction of exudate surrounding the brainstem or because of a brainstem tuberculoma that blocks drainage.

FORMS OF DISEASE — Forms of central nervous system (CNS) tuberculosis (TB) include tuberculous meningitis, tuberculoma, spinal arachnoiditis, and transverse myelitis.

Tuberculous meningitis — Issues related to tuberculous meningitis are discussed separately. (See "Tuberculous meningitis: Clinical manifestations and diagnosis" and "Central nervous system tuberculosis: Treatment and prognosis".)

Tuberculoma — A tuberculoma is a conglomerate granulomatous focus that develops from coalescing tubercles acquired during disseminated bacillemia. Tuberculomas occur most commonly in the brain; they may also occur in the spinal cord.

Clinical manifestations — Tuberculomas are often clinically silent and may reach considerable size in the absence of meningeal inflammation [23,24]. In the setting of TB meningitis, subclinical tuberculomas (single or multiple) may be observed on radiographic imaging. (See 'Tuberculous meningitis' above.)

Alternatively, tuberculoma may present as a clinically evident mass lesion of the brain in the absence of TB meningitis. This presentation occurs most commonly in endemic areas and typically consists of a child or young adult with headache, seizure, progressive hemiplegia, and/or signs of elevated intracranial pressure [25,26].

Tuberculomas may develop during adequate antituberculous therapy; this may be a result of the immune response against dying M. tuberculosis organisms.

Radiographic findings — Radiographically, tuberculomas are discrete, ring-enhancing lesions of the brain surrounded by perilesional edema; they may be single or multiple.

On contrast computed tomography imaging, radiographic findings of early-stage tuberculoma consist of low density or isodense lesions, often with edema out of proportion to mass effect and with little encapsulation (image 1) [25-27]. Later-stage tuberculomas are well encapsulated, isodense or hyperdense, and have peripheral ring enhancement.

On magnetic resonance imagining (MRI), tuberculomas appear hypointense on T1-weighted images and hyperintense on T2-weighted images (image 1). With contrast enhancement, there is either ring-shaped or homogeneous disc-shaped enhancement. 

In one meta-analysis including 404 patients with CNS TB, intracranial tuberculomas were observed on initial neuroimaging in 49 percent of cases; of these, multiple tuberculomas were observed in 78 percent of cases [18]. Innumerable small tuberculomas may be observed in patients with tuberculous meningitis associated with miliary TB (image 2).

Diagnosis — The diagnosis of tuberculoma should be suspected in patients with mass lesion of the brain and relevant epidemiologic factors (eg, history of prior TB infection or disease, known or possible TB exposure, and/or past or present residence in or travel to an area where TB is endemic).

Establishing a diagnosis of tuberculoma can be challenging. A presumptive diagnosis may be made in the setting of relevant clinical and epidemiologic factors and typical radiographic findings (see 'Radiographic findings' above), particularly if a definitive diagnosis of TB has been established from an extraneural site of disease (such as lung, gastric fluid, lymph nodes, bone marrow, or liver). (See "Diagnosis of pulmonary tuberculosis in adults" and "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis".)

A definitive diagnosis of tuberculoma is established via needle biopsy of the CNS lesion for histopathology and acid-fast bacilli (AFB) stain and culture; however, surgical intervention should be avoided as it may precipitate meningitis. In addition, lumbar puncture is usually avoided because of concern for elevated intracranial pressure and risk of brainstem herniation. For cases in which cerebrospinal fluid (CSF) is examined, findings may demonstrate elevated protein concentration, normal glucose concentration, and pleocytosis (10 to 100 cells/microL, typically lymphocyte predominant) [6].

Patients with suspected CNS TB should undergo chest radiography; in the setting of relevant signs or symptoms, diagnostic evaluation for pulmonary TB should be pursued. In addition, for patients with signs and symptoms of suggestive of TB at other sites, diagnostic evaluation should be pursued accordingly (such as lymph node biopsy, bone marrow biopsy); such interventions may be safer and more accessible than CNS-based diagnosis [6]. (See "Diagnosis of pulmonary tuberculosis in adults", section on 'Radiographic imaging' and "Tuberculous lymphadenitis" and "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

For patients with HIV and low epidemiologic risk and low clinical suspicion for TB, a trial of empiric treatment for toxoplasmosis (prior to proceeding with brain biopsy) may be useful in some circumstances. (See "Approach to the patient with HIV and central nervous system lesions", section on 'Empiric treatment against toxoplasmic encephalitis in select toxoplasma-seropositive patients'.)

Differential diagnosis — The differential diagnosis of tuberculoma includes:

●Neurocysticercosis – Neurocysticercosis (NCC) and tuberculoma share similar epidemiologic, clinical, and radiographic features. Distinction between these two entities requires careful attention to radiographic features (identification of a scolex within a cystic lesion is a pathognomonic radiographic finding for NCC) and thorough evaluation for evidence of extraneural TB. (See "Cysticercosis: Clinical manifestations and diagnosis".)

●Cryptococcoma – Cryptococcoma and tuberculoma share similar clinical and radiographic features. Cryptococcus gattii is more likely than Cryptococcus neoformans to cause cryptococcoma (of the lungs and/or brain); however, given that C. gattii is concentrated in the northwestern United States and southwestern Canada, this species has less epidemiologic overlap with TB than C. neoformans. In the absence of contraindication to lumbar puncture, CSF should be examined; routine studies should be performed, in addition to cryptococcal antigen, India ink staining, and fungal culture. Alternatively, brain biopsy may be warranted. (See "Cryptococcus gattii infection: Clinical features and diagnosis" and "Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in patients with HIV" and "Clinical manifestations and diagnosis of Cryptococcus neoformans meningoencephalitis in patients without HIV".)

●CNS toxoplasmosis – Toxoplasmosis is the most common CNS infection in HIV-infected patients with CD4 count <100 cells/microL who are not receiving appropriate prophylaxis. Patients typically present with headache, fever, and altered mental status; focal neurologic deficits or seizures are also common. A definitive diagnosis requires a compatible clinical syndrome, identification of ≥1 mass lesions on brain imaging, and detection of the organism in a biopsy specimen; for most patients a presumptive diagnosis is made to avoid a brain biopsy. (See "Toxoplasmosis in patients with HIV" and "Approach to the patient with HIV and central nervous system lesions".)

●Brain abscess – Clinical manifestations of brain abscess may be subacute and nonspecific. Lumbar puncture is contraindicated in patients with papilledema or focal symptoms or signs; if it is feasible to obtain CSF, findings may demonstrate elevated protein concentration, low glucose concentration, and pleocytosis. A microbiologic diagnosis may be established culture of material obtained via stereotactic-guided aspiration or surgery. (See "Pathogenesis, clinical manifestations, and diagnosis of brain abscess".)

●CNS lymphoma – CNS lymphoma is an important cause of CNS lesion in HIV-infected patients. Clinical presentation is typically acute to subacute, with symptoms such as confusion, lethargy, memory loss, hemiparesis, aphasia, and/or seizures progressing over days to weeks. The diagnosis is established via brain biopsy. (See "HIV-related lymphomas: Primary central nervous system lymphoma" and "Approach to the patient with HIV and central nervous system lesions".)

●Brain tumor (primary or metastatic brain) – Clinical manifestations of brain tumor include headache, seizures, focal deficits, cognitive dysfunction, and increased intracranial pressure. The diagnosis is suspected based on radiographic findings and confirmed via biopsy. (See "Overview of the clinical features and diagnosis of brain tumors in adults".)

Management — Issues related to management of tuberculoma are discussed separately. (See "Central nervous system tuberculosis: Treatment and prognosis", section on 'Tuberculoma'.)

Spinal arachnoiditis

Pathogenesis and epidemiology — Spinal tuberculous arachnoiditis develops in the context of breakdown of granulomatous foci within the spinal cord or meninges; in such cases, the spinal cord and spinal nerve roots are encased in tuberculous exudates. This can occur at any level of the spinal cord or by extension from an adjacent area of spondylitis [28,29]. (See "Bone and joint tuberculosis", section on 'Spondylitis (Pott disease)'.)

The resulting inflammatory reaction is usually confined locally and progresses gradually over weeks to months, producing a partial or complete encasement of the cord by a gelatinous or fibrous mass. A characteristic feature of tuberculous arachnoiditis, which differentiates it from other types of arachnoiditis, is its propensity to affect spinal cord, meninges, and nerve roots together in varying combinations [29].

Spinal tuberculous arachnoiditis occurs with variable frequency in patients with TB meningitis. In one series including 71 patients with TB meningitis, 46 percent had concomitant symptoms/signs of spinal cord and spinal nerve root involvement [29]. The most common site was the lumbosacral region (32 percent), followed by thoracolumbar (10 percent), thoracic (8.5 percent), and cervical (4 percent) regions. Risk factors for development of spinal cord involvement included long mean duration of illness prior to diagnosis and delay in initiation of antituberculous therapy.

Clinical manifestations — Clinical manifestations of tuberculous spinal arachnoiditis are protean. The most common presentation is an ascending or transverse radiculomyelopathy of variable pace, at single or multiple levels [28]. Tuberculous radiculomyelopathy may precede, coincide with, or follow (by months or years) an initial episode of TB meningitis.

Patients with spinal tuberculous arachnoiditis usually present with subacute onset of nerve root and cord compression signs. Symptoms include spinal or radicular pain, hyperesthesia or paresthesia in the distribution of the nerve root, upper or lower motor neuron paralysis, and bladder or rectal sphincter incontinence. Vasculitis may result in thrombosis of the anterior spinal artery and infarction of the spinal cord.

Some patients with unrecognized chronic, indolent spinal tuberculous arachnoiditis progress to frank TB meningitis as a late complication of disease. (See 'Tuberculous meningitis' above.)

Diagnosis — The diagnosis of spinal arachnoiditis should be suspected in patients with relevant clinical manifestations (subacute onset nerve root and cord compression signs) and relevant epidemiologic factors (history of prior TB infection or disease, known or possible TB exposure, and/or past or present residence in or travel to an area where TB is endemic).

A presumptive diagnosis of spinal arachnoiditis may be made in the setting of typical radiographic findings (spinal MRI with nodular arachnoiditis) and CSF examination (unusually high CSF protein levels, with or without pleocytosis), particularly if a definitive diagnosis of TB has been established from an extraneural site of disease (such as lung, gastric fluid, lymph nodes, bone marrow, or liver). (See "Diagnosis of pulmonary tuberculosis in adults" and "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis".)

Radiographically, spinal cord and spinal nerve root involvement manifests with diffuse enhancement of meninges overlying spinal cord and nerve roots. In tuberculous myelitis, there is T2/fluid-attenuated inversion recovery hyperintensity spreading over multiple segments [28-30].

In patients who present with signs and symptoms of meningitis as well as spinal cord involvement, CSF diagnostic studies (positive smear, positive nucleic acid amplification tests) may suffice for diagnosis. In patients with subarachnoid block, the CSF protein concentration may be as high as 2 g/dL; other CSF findings may include elevated protein concentration, normal glucose concentration, and pleocytosis (10 to 100 cells/microL, typically lymphocyte predominant). There are no data to establish the reliability of CSF examination for the diagnosis of isolated forms of spinal TB; in the absence of meningitis, a definitive diagnosis of spinal arachnoiditis is established via needle biopsy of the CNS lesion for histopathology and AFB stain and culture.

Patients with suspected TB should undergo chest radiography; in the setting of relevant signs or symptoms, diagnostic evaluation for pulmonary TB should be pursued. In addition, for patients with signs and symptoms of suggestive of TB at other sites, diagnostic evaluation should be pursued accordingly (such as lymph node biopsy, bone marrow biopsy); such interventions may be safer and more accessible than CNS-based diagnosis [6]. (See "Diagnosis of pulmonary tuberculosis in adults", section on 'Radiographic imaging' and "Tuberculous lymphadenitis" and "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

Differential diagnosis — Other presenting forms of spinal cord and nerve root involvement in the setting of tuberculosis include [28]:

●Spinal tuberculoma – A spinal tuberculoma is a granulomatous focus in the spinal cord that develops from coalescing tubercles acquired during disseminated bacillemia (image 3). Clinically, it presents with features suggestive of subacute transverse myelopathy, characterized by progressive limb weakness, sensory deficits, and bowel and bladder dysfunction. (See 'Tuberculoma' above.)

●Tuberculous spondylitis and vertebral osteomyelitis (Pott disease) – Tuberculous spondylitis and vertebral osteomyelitis represent a disease continuum; involvement may include the intervertebral joints, one or more vertebral bodies, and one or more intervertebral disc spaces. (See "Bone and joint tuberculosis".)

Other infectious causes of spinal cord and nerve root involvement include:

●Cytomegalovirus infection (CMV) – In HIV-infected patients, the most common cause of lumbosacral polyradiculopathy is CMV infection. The diagnosis is established via CSF evaluation, including assessment of CSF viral load. (See "AIDS-related cytomegalovirus neurologic disease".)

●Syphilis – Uncommonly, syphilitic meningitis may affect the spinal cord and cause meningomyelitis or hyperplastic pachymeningitis with polyradiculopathy. Diagnostic testing includes serum treponemal and nontreponemal tests and spinal fluid examination to assess for presence of pleocytosis, elevated protein concentration, and CSF Venereal Disease Research Laboratory tests. (See "Neurosyphilis".)

Noninfectious causes of spinal cord disorders and polyradiculopathy are discussed further separately. (See "Disorders affecting the spinal cord" and "Polyradiculopathy: Spinal stenosis, infectious, carcinomatous, and inflammatory nerve root syndromes" and "HIV-related lymphomas: Primary central nervous system lymphoma".)

Management — Issues related to management of spinal arachnoiditis are discussed separately. (See "Central nervous system tuberculosis: Treatment and prognosis", section on 'Spinal arachnoiditis'.)

Transverse myelitis — Transverse myelitis is acute segmental spinal cord inflammation that may occur in the setting of tuberculosis disease; it may coexist with tuberculous meningitis. (See "Tuberculous meningitis: Clinical manifestations and diagnosis", section on 'Complications'.)

The pathogenesis is uncertain; it has been proposed that tuberculous proteins may provoke an exaggerated immune response against neuronal tissues of the spinal cord [31,32].

Clinical manifestations — Patients with tuberculous myelitis present with acute transverse cord syndrome consisting of motor, sensory, and/or autonomic dysfunction. Motor symptoms include paraparesis or quadriparesis. Sensory symptoms include pain, dysesthesia, and paresthesia; a sensory level can be identified in most patients. Autonomic symptoms may include urinary urgency, bladder/bowel incontinence, difficulty voiding, incomplete bowel evacuation, and sexual dysfunction.

Clinical features of transverse myelitis are discussed further separately. (See "Transverse myelitis: Etiology, clinical features, and diagnosis", section on 'Clinical features'.)

Radiographic findings — MRI of the spinal cord in patients typically demonstrates a gadolinium-enhancing signal abnormality. Tuberculous myelitis frequently presents with longitudinally extensive transverse myelitis (LETM), which is characterized by contiguous inflammatory lesions of the spinal cord extending to three or more vertebral segments [31,33,34]. Meningeal enhancement may also be observed [32].

Diagnosis — The diagnosis of tuberculous myelitis should be suspected in patients with relevant clinical manifestations (acute or subacute development of neurologic signs and symptoms consisting of motor, sensory, and/or autonomic dysfunction) and relevant epidemiologic factors (history of prior tuberculosis [TB] infection or disease, known or possible TB exposure, and/or past or present residence in or travel to an area where TB is endemic).

The diagnosis of tuberculous myelitis may be established based on the following:

●Radiographic findings demonstrating spinal cord inflammation (in the absence of cord compression) in the form of longitudinally extensive transverse myelitis (LETM), which refers to complete or incomplete spinal cord dysfunction with a lesion on that involves three or more vertebral segments. (See "Transverse myelitis: Etiology, clinical features, and diagnosis".)

●CSF demonstrating inflammation [in tuberculous myelitis, CSF typically demonstrates very high protein concentration (>1000 mg/dL)]

●Evidence of tuberculosis disease [outside of CNS (such as positive sputum AFB smear, AFB culture, or nucleic acid amplification test), and/or within the CNS (such as positive CSF AFB smear, AFB culture, or nucleic acid amplification test)].

However, definitive diagnosis can be challenging, given suboptimal sensitivity and specificity of diagnostic tools.

Differential diagnosis — Other conditions that may present with LETM include:

●Neuromyelitis optica spectrum disorders (NMOSD) – NMOSD are inflammatory disorders of the central nervous system characterized by severe, immune-mediated demyelination and axonal damage predominantly targeting optic nerves and the spinal cord. Diagnostic criteria for NMOSD are outlined separately. (See "Neuromyelitis optica spectrum disorder (NMOSD): Clinical features and diagnosis".)

●Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease [MOGAD] - MOGAD is an inflammatory disease of the central nervous system (CNS) characterized by attacks of immune-mediated demyelination. Diagnostic criteria for MOGAD are outlined separately. (See "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Clinical features and diagnosis".)

●Autoimmune diseases - Autoimmune diseases (such as Sjögren's syndrome, systemic lupus erythematosus and autoimmune thyroid disorders) can manifest with acute transverse myelitis. These conditions are discussed separately. (See related topics).

Management — Issues related to management of tuberculous myelitis are discussed separately. (See "Central nervous system tuberculosis: Treatment and prognosis", section on 'Transverse myelitis'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and treatment of tuberculosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Tuberculosis (Beyond the Basics)")

SUMMARY

●Forms of disease and epidemiology

•Forms of disease – Forms of central nervous system (CNS) tuberculosis (TB) include tuberculous meningitis, tuberculoma, spinal arachnoiditis, and transverse myelitis.

•Epidemiology – In regions where the prevalence of TB is high and post-primary dissemination is common among children and young adults, all forms of CNS TB (tuberculous meningitis, intracranial tuberculoma, spinal tuberculous arachnoiditis, and transverse myelitis) are encountered relatively frequently. In regions where the prevalence of TB is low, extrapulmonary manifestations of TB are observed primarily in adults with reactivation disease, and the predominant form of CNS disease is meningitis. (See 'Epidemiology' above.)

●Tuberculous meningitis – Issues related to tuberculous meningitis are discussed separately. (See "Tuberculous meningitis: Clinical manifestations and diagnosis".)

●Tuberculoma

•Clinical manifestations – A tuberculoma is a conglomerate granulomatous focus that develop from coalescing tubercles acquired during disseminated bacillemia. Tuberculomas occur most commonly in the brain; they may also occur in the spinal cord. They may occur with or without overt manifestations (headache, seizure, progressive hemiplegia, and/or signs of elevated intracranial pressure), and with or without concomitant meningitis. (See 'Clinical manifestations' above.)

•Diagnosis – A presumptive diagnosis of tuberculoma may be made in the setting of relevant clinical and epidemiologic factors and typical radiographic findings (image 1) particularly if a definitive diagnosis of TB has been established from an extraneural site of disease. A definitive diagnosis is established via needle biopsy of the CNS lesion for histopathology and acid-fast bacilli (AFB) stain and culture; however, surgical intervention should be avoided as it may precipitate meningitis. In addition, lumbar puncture is usually avoided because of concern for elevated intracranial pressure and risk of brainstem herniation. (See 'Diagnosis' above.)

●Spinal arachnoiditis

•Clinical manifestations – Spinal arachnoiditis develops in the context of breakdown of granulomatous foci within the spinal cord or meninges; in such cases, the spinal cord and nerve roots are encased in tuberculous exudates. This can occur at any level of the spinal cord, or by extension from an adjacent area of spondylitis. Patients with spinal tuberculous arachnoiditis usually present with subacute onset of nerve root and cord compression signs; these manifestations may precede, coincide with, or follow (by months or years) an initial episode of tuberculous meningitis. (See 'Clinical manifestations' above.)

•Diagnosis – A presumptive diagnosis of spinal arachnoiditis may be made in the setting of typical radiographic findings (spinal magnetic resonance imaging with nodular arachnoiditis) and cerebrospinal fluid (CSF) examination (unusually high CSF protein levels, with or without pleocytosis), particularly if a definitive diagnosis of TB has been established from an extraneural site of disease. In the absence of meningitis, a definitive diagnosis of spinal arachnoiditis is established via needle biopsy of the CNS lesion for histopathology and AFB stain and culture. (See 'Diagnosis' above.)

●Transverse myelitis

•Clinical manifestations – Patients with tuberculous myelitis present with acute transverse cord syndrome consisting of motor, sensory, and/or autonomic dysfunction. Motor symptoms include paraparesis or quadriparesis. Sensory symptoms include pain, dysesthesia, and paresthesia; a sensory level can be identified in most patients. Autonomic symptoms may include urinary urgency, bladder/bowel incontinence, difficulty voiding, incomplete bowel evacuation, and sexual dysfunction. (See 'Clinical manifestations' above.)

•Diagnosis – The diagnosis may be established based on radiographic findings demonstrating spinal cord inflammation (in the absence of cord compression), CSF demonstrating inflammation, and evidence of tuberculosis disease [outside of CNS (such as positive sputum AFB smear, AFB culture, or nucleic acid amplification test), and/or within the CNS (such as positive CSF AFB smear, AFB culture, or nucleic acid amplification test). However, definitive diagnosis can be challenging, given suboptimal sensitivity and specificity of diagnostic tools. (See 'Diagnosis' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge John M Leonard, MD, who contributed to an earlier version of this topic review.